Keratitis caused by herpes simplex virus is the single most frequent cause of corneal opacities in the western world. The disease is characterized by an intense cellular infiltrate and may result in permanent eye damage and blindness. Some evidence suggests that the host response to viral antigens is responsible for the opacities. Studies have revealed that viral antigens may persist in the disease beyond the period in which infectious virus is isolated. The overall objective of this proposal will be, as with the currently funded project, to determine the role of infectious virus and specific viral antigens in the pathogenesis of herpetic stromal eye disease. The specific aims are based on the view that stromal keratitis is dependent on the outcome of three general types of interaction involving virus and viral antigens: 1) host elimination of virus-infected cells, 2) production, persistence, and elimination of infectious virus and viral antigens, and 3) formation and elimination of virus specific Ag-Ab complexes. Intrastromal infection of New Zealand white rabbits will be used as the disease model. Specific aims are: 1) To determine and characterize antibody and cellular-effector systems (lymphocytes and phagocytes) capable of destroying infected keratocytes. Emphasis will be placed on the role of phagocyte-mediated destruction in stromal disease. In vitro assays comprised solely of rabbit materials (keratocytes, antibody, effector cells) will be used to examine killing mechanisms and to monitor host responses. 2) To characterize expression of surface structures of infected keratocytes reactive with antibody and effector cells. Emphasis will be placed on expression and function of specific HSV glycoproteins and HSV-induced fc receptors. 3) Clearance mechanisms for virus and viral antigens produced during herpetic eye disease. The ability of neutrophils and other phagocytes to ingest and degrade virus and antigen-antibody complexes will be examined. 4) Effect of infectious virus on effector cell functions. This is a counterpart to the aim described in No. 1. Experiments will be performed to determine if infectious virus, noninfectious virions, and Ag-Ab complexes can cause dysfunction of effector cells responding to herpetic disease. 5) To determine the location of complete virions, specific HSV glycoprotein antigens, and virus-induced Fc receptors in tissue sections of infected corneas and to correlate those findings with manifestations of disease and histopathological findins.